A LINE-1 component to human aging: do LINE elements exact a longevity cost for evolutionary advantage?
A LINE-1 component to human aging: do LINE elements exact a longevity cost for evolutionary advantage?
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DOI：
10.1016/j.mad.2010.03.008
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发表时间：
2010-05
影响因子：
5.3
通讯作者：
McCaffrey TA
中科院分区：
文献类型：
--
作者：
St Laurent G 3rd;Hammell N;McCaffrey TA
Advancing age remains the largest risk factor for devastating diseases, such as heart disease, stroke, and cancer. The mechanisms by which advancing age predisposes to disease are now beginning to unfold, due in part, to genetic and environmental manipulations of longevity in lower organisms. Converging lines of evidence suggest that DNA damage may be a final common pathway linking several proposed mechanisms of aging. The present review forwards a theory for an additional aging pathway that involves modes of inherent genetic instability. Long interspersed nuclear elements (LINEs) are endogenous non-LTR retrotransposons that compose about 20% of the human genome. The LINE-1 (L1) gene products, ORF1p and ORF2p, possess mRNA binding, endonuclease, and reverse transcriptase activity that enable retrotransposition. While principally active only during embryogenesis, L1 transcripts are detected in adult somatic cells under certain conditions. The present hypothesis proposes that L1s act as an ‘endogenous clock’, slowly eroding genomic integrity by competing with the organism’s double-strand break repair mechanism. Thus, while L1s are an accepted mechanism of genetic variation fueling evolution, it is proposed that longevity is negatively impacted by somatic L1 activity. The theory predicts testable hypotheses about the relationship between L1 activity, DNA repair, healthy aging, and longevity.
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影响因子：
14.9
作者：
Farkash EA;Kao GD;Horman SR;Prak ET
通讯作者：
Prak ET
DOI：
10.1073/pnas.0831042100
发表时间：
2003-04-29
影响因子：
11.1
作者：
Brouha, B;Schustak, J;Kazazian, HH
通讯作者：
Kazazian, HH
影响因子：
64.8
作者：
COULONDRE, C;MILLER, JH;GILBERT, W
通讯作者：
GILBERT, W
影响因子：
5.8
作者：
Belgnaoui SM;Gosden RG;Semmes OJ;Haoudi A
通讯作者：
Haoudi A
DOI：
10.1196/annals.1354.033
发表时间：
2006-01-01
期刊：
UNDERSTANDING AND MODULATING AGING
影响因子：
--
作者：
Capri, Miriam;Salvioli, Stefano;Franceschi, Claudio
通讯作者：
Franceschi, Claudio